Electrophysiological evidence for a role of bradykinin in chemical nociception in the rat

Single nociceptive neurones were recorded in the L 1-L 3 region of the dorsal horn of the spinal cord in halothane anaesthetized intact rats. Subcutaneous formalin (50 μl of 5% solution) into the peripheral receptive field produces a biphasic activation of these neurones. The initial 1st peak of the response was unaltered by any of the treatments. However, the prolonged 2nd peak of the response was significantly reduced to a similar degree by 10 min pretreatment with 50 μg subcutaneous B4162 (a bradykinin B 2 receptor antagonist) and by prior desensitization of the receptive field with bradykinin. The putative bradykinin B 1 receptor antagonist des-Arg 9[Leu 8]bradykinin (DALB) applied subcutaneously (50 μg) 10 min prior to formalin had no effect on the subsequent responses to formalin implying that the B4162 and bradykinin desensitization effects occur via the B 2 receptor. Repeated subcutaneous injection of bradykinin (10 μl of a l mg/ml solution) was used to elicit responses in these dorsal horn neurones and these were shown to be antagonised by 50 μg B4162 suggesting that the effects of this compound on the formalin response are indeed due to its ability to inhibit bradykinin induced neuronal activity. These results provide electrophysiological evidence for a physiological role of bradykinin as a mediator in prolonged chemical nociception.